title: Hypoxia regulates endothelin-1 production by the inner medullary collecting duct.
abstract: Renal endothelin-1 (ET-1 ) production is increased by hypoxia and has been implicated in ischemia-induced renal hypoperfusion. Because the inner medullary collecting duct (IMCD) is a major source of ET- 1 in the kidney, and because ET- 1--in the setting of ischemic renal failure-may alter medullary perfusion, we sought to determine whether hypoxia modulated ET-1 production by IMCD cells. Primary cultures of rat IMCD cells were exposed to 21%, 3%, or 0%O2. IMCD ET-1 secretion significantly increased after exposure of cultures to 3% O2 (114.1% +/- 4.7% increase over control value) and 0%O2 (171.7% +/- 7.9% increase). ET-1 mRNA levels, as determined by reverse transcription-polymerase chain reaction, also increased 2.5-fold after 24-hour exposure to 0% O2. We speculate that a hypoxia-induced increase in IMCD ET-1 production plays a role in modulating renal medullary perfusion during ischemic renal failure.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center and the University of Utah School of Medicine, Salt Lake City 84148, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Miller
authors.forename: D E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000818:Animals; D046508:Culture Techniques; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D000860:Hypoxia / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger